The
translationally controlled tumor protein (TCTP) is a highly conserved
protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side,
tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different
cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic
proteins of the Bcl-2 family and the
p53 tumor suppressor protein. In this article, we draw attention to the role of TCTP in
cancer, especially, focusing on cell differentiation and
tumor reversion, a biological process by which highly tumorigenic cells lose their malignant phenotype. This
protein has been shown to be the most strongly downregulated
protein in revertant cells compared to the parental
cancer cells. Decreased expression of TCTP results either in the reprogramming of
cancer cells into reversion or apoptosis. As conventional
chemotherapy is frequently associated with the development of drug resistance and high toxicity, the urge for the development of new or additional scientific approaches falls into place. Differentiation
therapy aims at reinducing differentiation backward to the nonmalignant cellular state. Here, different approaches have been reported such as the induction of
retinoid pathways and the use of
histone deacetylase inhibitors. Also, PPARĪ³ agonists and the activation of the
vitamin D receptor have been reported as potential targets in differentiation
therapy. As TCTP is known as the
histamine-releasing factor, antihistaminic drugs have been shown to target this
protein. Antihistaminic compounds,
hydroxyzine and
promethazine, inhibited cell growth of
cancer cells and decreased TCTP expression of
breast cancer and
leukemia cells. Recently, we found that two antihistaminics,
levomepromazine and
buclizine, inhibited
cancer cell growth by direct binding to TCTP and induction of cell differentiation. These data confirmed that TCTP is an exquisite target for anticancer differentiation
therapy and antihistaminics have potential to be lead compounds for the direct interaction with TCTP as new inhibitors of human TCTP and
tumor growth.